Process of manufacturing cyclopentenone derivatives



Patented Oct. 23,, 1945 PROCESS OF MANUFACTURING CYCLO- PENTENONEDERIVATIVES Heinz Hunsdiecker, Cologne-Braunsfeld, Germany; vested inthe Allen Property Custodian No Drawing. Application August 20, 1940,Serial No. 353,425. In Germany January 4, 1939 10 Claims. (Cl. 260-586)The processes having become known up to now for the manufacture ofcyclopentenonederivatives can be divided into two groups. In the onethereof the process starts from a finished cyclopentene-nucleus orcyclopentanenucleus respectively. There is thus, obtained for instance,alkylcyclopentenones from the nitrosochlorides of the alkylcyclopenteneswhen these are treated with potassium acetate and acetic acid. Thisprocess is, however, not generally applicable, as the use ofdialkylcyclopentenes in which the double bond lies between thesubstituted nucleuscarbon atoms is not possible. The processpresupposes, furthermore, the indiflerence of the selected alkyl groupswith respect to nitrosylchloride and the like. Besides, the yield is inmost cases not satisfying.

The other of the above mentioned two groups starts from linearcompounds. There is, thus, obtained, for instance,methyl-alkyl-cyclopentenones if esters from laevulic acid and estersfrom a-halogenfatty-acids are used as starting materials (compare, forinstance, Helv. Chim. Act. VII, pages 256-257, 1924) Also this processis subjected to similar restrictions as that for the manufacture ofalkylcyclopentenones from alkylcyclopentenes. A particularly gravedrawback connected therewith in this case is the comparatively slightyield. Thus, Staudinger and Ruzicka have obtained only about 1 /2 gramsof methyl-amyl-cyclopentenone from 318 grams of ethyl-a-bromenanthateand 182 grams of ethyllaevulinate (see also Treif and Werner, Berichte68, pages 642-643, 1935).

o 0011 the C groups excludes the formation of a cyclo 5 (mac 0 CH CH0 0CHR pentenone nucleus.

I have discovered that, in a surprising contrast to the hitherto usualopinion, the 'y-dicetones are able to form a cyclopentenone nucleus if amethyl-group is in a position adjacent to one of CHs.C O.CH:.CH:.CO.

the two (JO-groups but a methylene-group in a position adjacent to theother of the CO-groups, that is to say, if the 'y-dicetones correspondto the formula In this formula R1, Ra, R3, R4 denote hydrogen or anyother desired univalent group, 1. i. methyl, carboxyl or the like. R5 isan univalent aliphatic or aromatic or a substituted group.

The ring closure itself is a very simple operation. In many cases oneobtains a practically quantitative yield, if the procedure is carriedout CH3 CF:

Thus, cyclopentenonederivatives are obtained when the followingcompounds are used as starting materials:

(R=methyl, ethyl etc.) OHS-C consents 0 .CHz.CHz.OH:.CH2Br(Cl, J)omcocncmcocnm Ha CHsC O CHzCHC 0 (311211 E: CHaCOCH CHCOCHlR Ha Ha-CHaCO CHzCHCO CHzR etc.

Concerning the condensation agents it is most suitable to the object inview to make use or an aqueous, alcoholic or methyl-alcoholic potassium"hydroxide solution, sodium-hydroxide or barium hydroxide solution,furthermore of a solution 01' alkali-alcoholates, alkaline earthhydroxides, a1- kali-carbonate or alkali-bicarbonate or of a solution ofa similar substance, but it is as well possible to employ occasionallyaqueous or non-aqueous acids or solutions of acids, salts or the like.Finally, it is possible to carry out the reaction in the gas-phase, thevapor of the dicetone being then subjected to the action of heat, may bewith the simultaneous use of dehydrating agents.

The process constituting the present invention is more fully describedin detail in the following examples:

First example 5.9 grams oi. 2.5-nonane-dione (B. P.m= 1l2-114) areheated to boiling temperature together with 76 grams of 2%-aqueoussodium hydroxide solution, the mixture being kept at that temperaturefor several hours. There are obtained 4.15 grams of3-methyl-2-propylcyclopentene-2-=one-1, which are 80% of the theoreticalyield.

B. P.11,5=94,5 Semicarbazone: M. P. 212

, Second example 4.4 grams of 2.5-decandione (B. P.17= 132-134) areheated with 52 grams of 3%- aqueous potassium hydroxide solution toboiling, the mixture being maintained boiling for some time. The oilylayer is taken up by means of ethyl ether and is distilled invacuo afterthe ether has been evaporated. There are obtained 2.9 grams, viz. 74% ofthe theoretical yield of 3-methyl-2-butyl-cyclopentene-2-one-1 which isa liquid with an agreeable smell.

B. P.12=107 Semicarbazone: M. P.=193-193.5

Third example In a similar manner as in the first and in the secondexample there are obtained from 9.2 grams undecandione (B. P.14=141, M.P.=33) 7.6 grams, viz. 92% of the theoretical yield of3-methyl-2-n-amylcyclopentene-2-one-l. This product is dihydrojasmone,as appears from its analysis and its physical constants.

f.: H=10.96 (1:79.28 calc.: H=10.92 :79.45

The boiling point of the ketone purified by the semicarbazone is120-12l.5 at 12 mm.

The semicarbazone did not show any fusing point depression together witha dihydroj asmonesemicarbazone manufactured according to Duden andFreitag.

Fourth example If 6 grams of 2 methyldecandione-6.9

(B. P.1a=128-l32) are heated together with 65 With higher molecular'y-dicetones it is recommendable to make use of somewhat strongercondensation agents, an addition of alcohol, more concentratedsolutions, solid alkalior a condition, as the success is the same byheating for a longer period with dilute solutions.

Fifth example 2.2 grams of 2.5-dodecandione (B. P.1z== 148 M.P.=39.5-40.5, semioarbazone: M. P'.= 187) are stirred with 11 grams ofhot 3%-potassium hydroxide solution for several days. After cooling andextracting with ethyl-ether there are obtained 1.6 grams, viz. of thetheoretical yield, of 3-methyl-2-hexylcyclopentene-2-one-1.

B. P.1s=142-144 Semicarbazone: M. P.=l63.5-l64.5'

Sixth example A mixture oi. 3.6 grams of 2.5-tetradecandione' (M.P.=50-51), 20 com. of a 10%-potassium hydroxide solution and 30 ccm. ofalcohol is heated to boiling and maintained at this temperature for 2hours, whereaiter the alcohol is distilled-oil and the oily layer istaken up by ethyl-ether. Yield: 2.7 grams of3-methyl-2-octylcyclopentene-Z-one-l, which are 81.4% of the theoreticalyield.

Liquid of floweryodour; B. P.1:=157-160 Semicarbazone: M. P.=159-159.5

Seventh example A solution of 4.9 grams of 2.5-octadecandione (M.P.=70.5) in 30 ccm. of alcohol is heated to boiling together with 20com. of a 50%-aqueous potassium hydroxide solution, this temperaturebeing maintained for 1 hour. There are obtained 3.1 grams of3-methyl-2-dodecylcyclopentene-Z-one-l, which are 66% of thetheoreticalyield.

M. P.=34-'i5.5 B. P.2.5=171-173 Semicarbazone: M. P.=15l.5-152.5

Eighth example When ll-methoxy-2.5-undecandione is heated with a mixtureof 40 com. of a 5%-aqueous sodium hydroxide solution and 10 com. ofalcohol 3 methyl- 2- (e-methoxyamyl) -cyclopentene-2- one-l is obtained.

B. P.i4=146-148 Semicarbazone; M. P.=l50-150.5

Ninth example 11.5 grams of 7-methyl-4.7-diketoheptoic acid (M.P.=76-'78) are dissolved in 200 ccm. of potassium hydroxide solution,the mixture being then heated to boiling for 2 hours. The originallycolorless solution becomes somewhat darker. The mixture is cooled andneutralised with an amount of sulphuric acid accurately equivalent t theamount of the potassium hydroxide solution. Then the aqueous solution isconcentrated by evaporation and the residueis extracted withethyl-acetate. After the ethylacetate has evaporated there are obtained10 grams instead of, theoretically, 10.3 grams of 3- methyl cyclopentene2 one-1-acetic-acid-2. After the recrystallisation of this product fromethyl acetate this acid forms stout Crystals of M. P.=108.5-110.5Semicarbazone: M. P.=2l3.5-216 (decomposition) Tenth example From 11methyl 4,7 diketoundecanoic acid steamer M. 12:63-65. Equivalentweight=212 instead of 210 Eleventh example The condensation product ofsodium salt of propionyl-acetic-acid-ester and bromoacetone is heatedfor some time together with an excess of 2%sodium solution. The esterforms the corresponding y-dicetone and this reacts by ring closuresimilarly to that described in the preceding example. There is obtained2,3'-dimethylcyclo-pentene-2-one-l.

Liquid of B. P.1e=7578 Semicarbazone: M. P.=247.5 (decomposition)Twelfth example 25 grams of a-capronyl-laevulic acid-ethylester aregradually heated with 1 liter of 2% sodium iwdroxide solution toboiling, neutralised after a short period of boiling and then extractedwith ethyl-ether. There are obtained 10.7 grams, equal to 73.3% of thetheoretical yield,.of 3- methyl-2-butylcyclopentene-2-one-1 of B.P.m=102-107 Semicarbazone: M. P.=192

Thirteenth example In correspondence with the description concerning thepreceding example 42.5 grams of a-heptene-(4)-oyl-laevulicacid-ethyl-ester are heated together with a 2%-sodium hydroxide solutionto boiling. A sufllcient quantity of acid is added and the productextracted with ethylether. There are obtained 17.6 grams=65% of thetheoretical yield of 3-methyl-2-(penten-2- yl)-cyc1opentene-2-0ne-1. B.P.e=122. The

product is identical with the natural lasmone.

In a similar manner it has been possible to obtain the correspondinghexylcyclopentenonederivates from the a-enanthoyland thea-caprylyl-laevulic acid ethyl-ester.

Fourteenth example 25 grams of a-capronyl-p-methyl-laevulicacidethyl-ester have been treated in the manner described in the twelfthexample. There has been obtaind the 3Z4-dimethyl-2-butylcyclopentene-2-one-1.

Liquid of B. P.14=1l4-115. Semicarbazone: M. P.=230-232 (decomposition)There have, furthermore, been obtained from a-caprony1--methyl-1aevulicacid ethyl ester the 3.5 dimethyl-2-butylcyc1opentene-2-one-l. Liquid ofB. P.11=104.

Fifteenth example Sixteenth example 2.5-undecandione is slowly distilledover sillcagel containing a little alkalihydroxide and Seventeenthexample A mixture of 50 grams of cold saturated p0- tassium-carbonatesolution, 30 com. of alcohol and 4 grams of 2.5-dodecandione is heatedunder shaking in a sealed tube for at least one day to to 140". Aftersettling of the process there are obtained about 80%, of the theoreticalyield of 3-methyl-2-hexylcyclopentene-2-one-1.

Eighteenth example 4 grams of dodecandione are dissolved in 50 com. of nmethyl-alcoholic barium hydroxide solution and are kept boiling for 2 or3 hours. There is obtained a yield of 64% of 3-:methy1-2-hexylcyclopentene-2-one-1.

B. P.1e=-137 Nineteenth example 2 grams of sodium metal are dissolved in40 grams of anhydrous methanol, whereaiter 17 grams of acetic ester and4 grams of dodecandione are added. The acetic ester is partiallysaponificated by the water split off during the reaction. In this casesodium methylate is the condensation agent. There are obtained 2.8grams, viz. 77% oi the theoretical yield, of 3-methyl-2-hexylcyclopentene-2-one-1.

The products obtained by the present im-' proved'process are intendedfor use as perfumes, means for annihilating plant lice and other noxiousanimals, etc., for the synthesis of curatives, etc., and the like.

I claim:

1. The process of making substituted cyclopenteneones which comprisescyclizing diketones oi the iormula CHI-C 0.011-011-0 01mm;

in which R1 is a monovalent substituent selected from the groupconsisting oi hydrogen and methyl, Ra is selected from the groupconsisting or hydrogen, methyl and carboxyl and R3 is a radical selectedfrom the group consisting of alkyl, halogenalkyl, carboxyl-alkyl,esterified carboxyl-alkyl, hydroxy-alkyl and ,alkyloxyalkyl, by treatingthe same with an alkali.

2. The process of making substituted cyclopentenones which comprisescyclizing diketones of the formula in which R2 is a monovalentsubstituent selected from the group consisting of hydrogen, methyl andcarbonyl and R3 is a radical selected from the group consisting ofalkyl, halogen-alkyl, carboxyl-alkyl, esterifled carboxyl-alkyl.hydroxyalkyl and alkyloxy-alkyl by treating the same with an alkali.

3. The process of substituted cycloalkyl,

pentenones which comprises cyclizing diketones of the formulaoniooonomooomn:

in which R1 is a substituent selected from the group consisting ofhydrogen and methyl and R3 is a radical selected from the groupconsisting of alkyl, halogewalkyl, carboxyl alkyl, esterified .carboxylalkyl, hydroxy-alkyl and alkyloxy-alkyl by treating the same with analka 4. The process of 'making substituted cyclopentenones whichcomprises cyclizing diketones oi the formula.

CHa.CO.CI-I2.CH2.CO.CH2R3 c in which R: is a radical selected from thegroup consisting of alkyl, halogen-alkyl, carboxylesterifledcarboxyl-alkyl, hydroxy-alkyl and alkyloxy-alkyl by treating the samewith an alkali.

5. The process of making substituted cyclopentenones which comprisescyclizlng diketones ot the formula omcocmcmcoomn in which R. is an alhrlradical, by treating the same with an alkali.

6. The process of making substituted cyclopentenones which comprisescyclizing ,diketones oi the formula cmcocmcmcocmn) in which R. is acarboxyl-alkyl radical. by treating the same with an alkali.

7. The process which comprises cyclizing 7- methyl-4,'l-'diketoheptoicacid, by treating the I same with an alkali.

